This project proposes to define the role of immune suppression of erythropoiesis in the pathogenesis of hemolytic disease of the newborn and warm-type autoimmune hemolytic anemia, and to test the hypothesis that the Ph antigen complex is a key membrane receptor in immunologically mediated inhibition of erythropoiesis. An understanding of the antigenic composition of hematopoietic stem cell and early erythroid precursors is basic to any attempt to elucidate the mechanisms involved in immune injury. The D antigen is a unique marker for erythropoietic tissue and as such provides an ideal model system for study. We will quantitate the expression of the D antigen in the differentiating plasma membrane in both adult and fetal tissue using an 125I-anti-D-autoradiographic method, and further define the nature of this antigen in the nucleated red cell precursor with respect to enzymatic modification, lateral mobility in the plane of the membrane, and complement fixation. The methylcellulose technique to culture erythroid elements in vitro will be applied to demonstrate the expression, if any, of the D antigen on erythroid stem cells, and to determine wheter anti-D or autoantibody mediated suppression of erythropoiesis can be demonstrated in vitro. These studies are designed to help us understand better the pathophysiology of clinically-significant hemolytic disorders, with the hope that the knowledge gained may open the way for a fresh approach to their management.